Hormonal changes and increased anxiety-like behavior in a perimenopause-animal model induced by 4-vinylcyclohexene diepoxide (VCD) in female rats.

Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.

Structure-mutagenicity relationships in 2-furylethylene derivatives. A molecular orbital study of the role of nitro groups.

An analysis of the electronic molecular structure of 2-furylethylene derivatives is carried out using a molecular orbital method. The differences in the electronic features of the nitro groups at two different positions of the furylethylene framework are well-accounted for in the present study. It is shown that nitro groups at position 5 of the furan ring of these compounds are more sensible to reduction in biological media that those at position beta of the exocyclic double bond. This greater sensitivity to reduction of 5-nitro compounds is given by the atomic and group charges on nitro group as well as for the low values of the energy of the lowest unoccupied molecular orbital. Discriminant functions able to classify 2-furylethylenes as mutagenic or not mutagenic are also obtained. These functions permitted the classification of 2-furylethylenes having or not nitro group in their structures. Finally, some quantitative models that describe the mutagenic potency of active compounds in terms of electronic molecular parameters were obtained. In all cases the models developed are in complete agreement with the experimental findings reported for this kind of compounds.